Efficient Strategies for Microglia Replacement in the Central Nervous System

Zhen Xu; Yanxia Rao; Yubin Huang; Tian Zhou; Rui Feng; Shanshan Xiong; Ti-Fei Yuan; Shan Qin; Yijie Lu; Xin Zhou; Xiaoyu Li; Bo Qin; Ying Mao; Bo Peng

doi:10.1016/j.celrep.2020.108041

Efficient Strategies for Microglia Replacement in the Central Nervous System

Cell Rep. 2020 Aug 11;32(6):108041. doi: 10.1016/j.celrep.2020.108041.

Authors

Zhen Xu¹, Yanxia Rao², Yubin Huang¹, Tian Zhou¹, Rui Feng¹, Shanshan Xiong¹, Ti-Fei Yuan², Shan Qin³, Yijie Lu³, Xin Zhou⁴, Xiaoyu Li⁵, Bo Qin⁶, Ying Mao⁴, Bo Peng⁷

Affiliations

¹ Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
² Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 201108, China.
³ Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Shenzhen Aier Eye Hospital, Shenzhen 518032, China.
⁴ Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontier Center for Brain Science, Fudan University, Shanghai 200032, China.
⁵ Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontier Center for Brain Science, Fudan University, Shanghai 200032, China; School of Biomedical Engineering, Capital Medical University, Beijing 100069, China.
⁶ Shenzhen Aier Eye Hospital, Shenzhen 518032, China.
⁷ Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontier Center for Brain Science, Fudan University, Shanghai 200032, China; Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu 226001, China. Electronic address: bopeng@connect.hku.hk.

PMID: 32783928
DOI: 10.1016/j.celrep.2020.108041

Abstract

Microglia are important immune cells in the central nervous system (CNS). Dysfunctions of gene-deficient microglia contribute to the development and progression of multiple CNS diseases. Microglia replacement by nonself cells has been proposed to treat microglia-associated disorders. However, some attempts have failed due to low replacement efficiency, such as with the traditional bone marrow transplantation approach. In this study, we develop three efficient strategies for microglia replacement: microglia replacement by bone marrow transplantation (mrBMT), microglia replacement by peripheral blood (mrPB), and microglia replacement by microglia transplantation (mrMT). mrBMT and mrPB allow microglia-like cells to efficiently replace resident microglia in the whole CNS. On the other hand, mrMT achieves microglia replacement in brain regions of interest. In summary, the present study offers effective tactics for microglia replacement with diverse application scenarios, which potentially opens up a window on treating microglia-associated CNS disorders.

Keywords: CSF1R; allograft; allotransplantation; bone marrow transplantation; fate mapping; microglia; parabiosis; replacement; repopulation; transplantation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Central Nervous System / physiopathology*
Central Nervous System / surgery
Humans
Mice
Microglia / transplantation*